Sickle cell disease (SCD) often results in acute vaso-occlusive crisis (VOC), an obstruction
of blood vessels resulting in ischemic injury and pain. The pain experienced during these
episodes is due to a wide range of pathophysiological processes. Though recent studies have
begun to unravel the underlying mechanisms of these processes, literature focused on pain
management for sickle cell disease is scarce. Opioids and non-steroidal anti-inflammatory
drugs (NSAIDs) remain the predominate treatment for VOC.
However, the efficacy of these treatments has come into question. A large sub-set of patients
with SCD report continued pain despite treatment with opioids. Tolerance and opioid-induced
hyperalgesia (OIH) may be responsible for unresponsiveness to opioid-centric treatment
modalities. New classes of drugs are being tested to prevent and treat acute pain associated
with SCD, but in the meantime physicians are looking to existing therapies to bridge the gap.
The N-methyl-d-aspartate (NMDA) receptor has been implicated in both tolerance and OIH. As a
NMDA receptor agonist, ketamine has been shown to modulate opioid tolerance and OIH in animal
models and clinical settings. Ketamine utilized as a low dose continuous infusion could
benefit patients with SCD related pain that are unresponsive to opioid analgesics. Based on
limited studies of adjuvant ketamine use for pain management, low-dose ketamine continuous
infusion appears safe. Further clinical investigations are warranted to fully support the use
of low-dose ketamine infusion in patients with SCD-related pain.